The invention relates generally to affinity binders (e.g. antibodies, peptides, etc) that undergo a change in affinity upon exposure to environmental cues.
As the state of biological research, technologies, and medicine advances, there is an increasing need for improved compositions and methods to probe and/or manipulate biological manner in a gentle, non-biasing fashion. For example, the emerging field of cell therapy will soon require the ability to positively identify, purify, and administrate desired cells in a manner that leaves them unmodified and unactivated to minimize the risk of complications or non-efficacious treatment. Strategies to assist in this identification and purification typically rely on specific, high affinity antibodies. DETACHaBeads (Dynal/Invitrogen), for example, are a commercially available product that captures B and T cells onto antibody-coated magnetic beads. To assist in administration, cell release is then achieved through input of a second antibody that competitively binds to the first antibody and releases cells. Another product, the Isolex Magnetic Cell Selection System (Baxter) relies on a similar approach to capture CD34+ stem cells onto magnetic beads. Cell liberation in this instance, however, occurs with the addition of a release peptide that competitively binds to a bead-bound secondary antibody. Despite the proven utility of these systems, the necessity to add additional reagents increases time, cost and has the potential to contaminate cell product with the added antibody or peptides.
Similarly, in the screening of biological samples for disease diagnosis and treatment determination, as well as in sensors for biological or defense applications, target identification is limited by the use of classical high-affinity binders, such as antibodies, which are difficult to remove without damaging the samples and reducing or eliminating the ability for further analysis. Due to these limitations, there remains a strong impetus to develop a next generation platform for biological identification and manipulation that retains the functional superiority of specific, high affinity target binding, but which enables target release upon command in a manner that leaves the biological sample intact and unmodified.